Lactic acid bacteria capable of preventing and/or treating senescence and dementia

ABSTRACT

The present invention provides a novel lactic acid bacterium having antioxidant and anti-aging functions and a dementia alleviation effect, and more specifically, provides Lactobacillus pentosus var. plantarum C29 KCCM11291P and Lactobacillus curvatus C3 KCCM430009. In addition, the present invention provides an antioxidant and anti-aging pharmaceutical composition and a dietary supplement containing the Lactobacillus pentosus var. plantarum C29 KCCM11291P or Lactobacillus curvatus C3 KCCM430009 of the present invention as an active ingredient, and a composition for preventing or treating dementia and a dietary supplement for preventing or alleviating dementia, containing Lactobacillus pentosus var. plantarum C29 KCCM11291P or Lactobacillus curvatus C3 KCCM430009 as an active ingredient. Additionally, the present invention provides a composition for preventing or treating dementia, containing a fermentation composition, as an active ingredient, fermented by Lactobacillus pentosus var. plantarum C29 KCCM11291P or Lactobacillus curvatus C3 KCCM430009.

CROSS REFERENCE TO RELATED APPLICATION

This Application is a division of U.S. patent application Ser. No.14/421,714, filed Feb. 13, 2015, which is a 371 Application ofInternational Application No. PCT/KR2013/007410, filed Aug. 16, 2013,which claims the benefit of Korea Patent Application No.KR10-2012-0089714, filed Aug. 16, 2012, the disclosures of which areincorporated herein in their entirety.

BACKGROUND Technical Field

The present invention relates to a novel lactic acid bacterium isolatedfrom Kimchi, and more specifically, relates to novel Lactobacilluspentosus var. plantarum C29 and Lactobacillus curvatus C3 having anactivity for preventing and/or treating aging (senescence) and dementia.

Background Art

To delay an aging process is one of important health challenges in amodern society rapidly proceeding into an aging society. In Korea, thepopulation aged 65 or more comprised 11.3% in 2010, and is anticipatedto rapidly increase to 37.3%. In such the aging society, it isanticipated that a disease morbidity rate is increased and enormousmedical expenses are expected, as well as it is anticipated that a rapidgrowth of senile disease such as dementia becomes to be problematicsocially.

A process progressing the aging is affected by a genetic, environment,and complex action of a lifestyle, and is followed by variousmorphological, biochemical changes, in particular, an increase ofoxidation stress and inflammation reaction are believed as a majorreason involving in a promotion of aging. The oxidation stress is causedby an increase of a generation of reactive oxygen species having astrong reactivity or a reduction of an anti-oxidative defense mechanismin a body, and as a result, biomacromolecules such as DNA, etc. aredestroyed, cellular damages are caused to promote the aging, and a riskof age-associated diseases, such as degenerative neuronal diseaseincluding dementia, cancer, cardiovascular diseases, etc. is increased.

Alder et al. (Adler A S, Sinha S, Kawahara T L, Zhang J Y, Segal E,Chang H Y. Motif module map reveals enforcement of aging by continuousNF-kappa B activity. Genes Dev. 2007; 21:3244-57) proved a relevancebetween NF-κB activation motif and a unit regulating the aging processand thus demonstrated that the inflammation reaction mediated by NF-κBand the aging process are very closely associated with each other. Inaddition, it is known that the aging activates PI3K/AKT, whichphosphorylates FOXO3, and ROS generation cannot be inhibited and thus agene variation, etc. are occurred.

Dementia which is one of aging diseases is occurred by chronic orprogressive diseases of brain, and regression, degeneration of braintissues, and aging-central nervous system infection (neurosyphilis,tuberculous meningitis, viral encephalitis, etc.), cerebral infarction,brain damage, toxic metabolic disorder, nervous system disease(Parkinson's disease) and the like, have been known to be a major reasonfor causing the dementia. Dementia includes Alzheimer's disease,vascular dementia, and other mixed forms, 50˜60% of old dementiapatients aged 65 or more have Alzheimer's dementia and remaining 10˜15%of them have the mixed forms of such two (2) diseases. It is known thata waste in brain, β-amyloid (Aβ) is a major cause of the disease ofAlzheimer-type dementia, and many drugs have been attempted for treatingAlzheimer-type dementia but there are no drug proving its significanteffects. Only acetylcholinesterease inhibitor which acts inacetylcholine, is used as a treating agent, but it is known that itpartially exhibits an improvement of a cognitive function but doesabsolutely no action in proceeding of Alzheimer's disease. And thus,there is a need for a development of the effective agent for preventingor treating dementia.

Meanwhile, lactic acid bacteria have been used for a long time and theirintestinal regulations, anticancer effects, immune boost effects and thelike have been reported. Therefore, inventors of the present inventionhad been studied for searching lactic acid bacteria having beneficialeffects in aging and dementia, and as a result, confirmed that novellactic acid bacteria isolated from Kimchi have effects for preventing ortreating aging and dementia and then completed the present invention.

SUMMARY

An object of the present invention is to provide lactic acid bacteriahaving effects for preventing or treating an aging and dementia.

In addition, another object of the present invention is to provide anantioxidant and anti-aging composition and a composition for preventingor treating dementia, which include the lactic acid bacteria.

Furthermore, still another object of the present invention is to providean antioxidant and anti-aging fermentation composition, and afermentation composition for preventing or treating dementia, which arefermented with the lactic acid bacteria.

To achieve said objects, the present invention provides Lactobacilluspentosus var. plantarum C29 KCCM11291P isolated from Kimchi.

In addition, the present invention provides an antioxidant andanti-aging pharmaceutical composition including Lactobacillus pentosusvar. plantarum C29 as an active ingredient.

In addition, the present invention provides a pharmaceutical compositionfor preventing or treating dementia, which includes Lactobacilluspentosus var. plantarum C29 as an active ingredient.

In addition, the present invention provides a health dietary supplementhaving antioxidant and anti-aging effects, which includes Lactobacilluspentosus var. plantarum C29 as an active ingredient.

In addition, the present invention provides a health dietary supplementfor preventing or improving dementia, which includes Lactobacilluspentosus var. plantarum C29 as an active ingredient.

In addition, the present invention provides an antioxidant andanti-aging composition including a fermentation composition, which isfermented with Lactobacillus pentosus var. plantarum C29, as an activeingredient.

In addition, the present invention provides a composition for preventingor treating dementia, which includes a fermentation composition that isfermented with Lactobacillus pentosus var. plantarum C29, as an activeingredient.

In addition, the present invention provides Lactobacillus curvatus C3KCCM43009 isolated from Kimchi.

In addition, the present invention provides an antioxidant andanti-aging pharmaceutical composition including Lactobacillus curvatusC3 as an active ingredient.

In addition, the present invention provides a pharmaceutical compositionfor preventing or treating dementia, which includes Lactobacilluscurvatus C3, as an active ingredient.

In addition, the present invention provides a health dietary supplementhaving antioxidant and anti-aging effects, which includes Lactobacilluscurvatus C3, as an active ingredient.

In addition, the present invention provides a health dietary supplementfor preventing or improving dementia, which includes Lactobacilluscurvatus C3, as an active ingredient.

In addition, the present invention provides an antioxidant andanti-aging composition including a fermentation composition, which isfermented with Lactobacillus curvatus C3, as an active ingredient.

In addition, the present invention provides a composition for preventingor treating dementia, which includes a fermentation composition that isfermented by Lactobacillus curvatus C3, as an active ingredient.

BRIEF DESCRIPTION OF DRAWINGS

FIG. 1 illustrates the 16S rDNA sequence of C29 lactic acid strain (SEQID NO. 1).

FIG. 2 is a phylogenetic tree illustrating a position of Lactobacilluspentosus var. plantarum C29.

FIG. 3 is a graph illustrating the results of a passive avoidanceresponse task.

FIG. 4 is a graph illustrating the effect of a C29 strain on improvingmemory that is increased in a concentration-dependent manner.

FIG. 5 is a gel photograph illustrating the effect of a C29 strain onimproving memory.

FIG. 6 is a graph illustrating the results of a Y-maze task in Example2.

FIG. 7 is a graph illustrating the result of a water maze task inExample 2, in which a black square represents scopolamine+(1×10⁹ colonyforming unit (CFU)/mouse C29), a white square representsscopolamine+(1×10¹⁰ colony forming unit (CFU)/mouse C29), a blacktriangle represents scopolamine+(10 mg/kg of tacrine positive controldrug), a white circle represents only scopolamine, and a black circlerepresents the normal control mice. The value is an average±SEM (n=6).

#p<0.05 vs. normal control, *p<0.05 vs. scopolamine single treatmentcontrol.

FIG. 8 is a gel photograph illustrating a change in an amount of theexpression of aging-associated gene phosphate according to theadministration of a C29 strain.

FIG. 9 is a graph illustrating the results of a Y maze task in Example3, in which Y represents the young mice, O represents the aged mice,O/C29 represents the aged mice administered with C29 lactic acidbacteria (1×10⁹ colony forming unit (CFU)/mouse), O/C3 represents theaged mice administered with C3 lactic acid bacteria (1×10⁹ colonyforming unit (CFU)/mouse), and O/C24 represents the aged miceadministered with C24 lactic acid bacteria (1×10⁹ colony forming unit(CFU)/mouse).

FIG. 10 is a graph illustrating the results of a water maze task inExample 3, in which Y represents the young mice, O represents the agedmice, O/C29 represents the aged mice administered with C29 lactic acidbacteria (1×10⁹ colony forming unit (CFU)/mouse), O/C3 represents theaged mice administered with C3 lactic acid bacteria (1×10⁹ colonyforming unit (CFU)/mouse), and O/C24 represents the aged miceadministered with C24 lactic acid bacteria (1×10⁹ colony forming unit(CFU)/mouse). The value is an average±SEM (n=6).

FIG. 11 illustrates 16S rDNA sequence (SEQ ID NO. 2) of C3 lactic acidbacteria.

FIG. 12 is a graph illustrating the cognitive function-improvementeffect of the fermentation composition fermented by a C29 strain or C3strain.

DETAILED DESCRIPTION

The Lactobacillus pentosus var. plantarum C29 and Lactobacillus curvatusC3 of the present invention are novel microorganisms isolated fromcabbage Kimchi.

The Lactobacillus pentosus var. plantarum C29 of the present inventionis a strain belonging to lactobacillus in a molecular phylogeneticsystematic and biochemical characteristic analysis based on 16s rDNAbase sequence and was identified as the strain exhibiting a high levelof the molecular phylogenetic systematic relationship with both ofLactobacillus pentosus and Lactobacillus plantarum, but since itsbiochemical characteristics were more similar to those of Lactobacilluspentosus, it was called as Lactobacillus pentosus var. plantarum C29,and deposited, in compliance with the Budapest Treaty on theInternational Recognition of the Deposit of Microorganisms for thePurpose of Patent Procedure, on the International Depository Authority,Korean Culture Center of Microorganisms (“KCCM”) as a Deposit No.KCCM1129P, on Jul. 9, 2012. The deposit was accepted as viable on Apr.10, 2015. KCCM has an address of 361-221, Yurim B/D, Hongje-1-dong,Seodaemun-gu, SEOUL 120-091, Republic of Korea.

In addition, since the Lactobacillus curvatus C3 of the presentinvention is a strain belonging to lactobacillus in the molecularphylogenetic systematic analysis based on 16s rDNA base sequence, andwas identified as the strain belonging to Lactobacillus curvatus, andthus, it was called as Lactobacillus curvatus C3, and deposited on theInternational Depository Authority, KCCM as a Deposit No. KCCM43009, onJul. 9, 2012.

The Lactobacillus pentosus var. plantarum C29 (hereinafter, alsoreferred to as “C29”) and the Lactobacillus curvatus C3 (hereinafter,also referred to as “C3”) of the present invention were identified ashaving effects on improving a memory of mice by a passive avoidanceresponse test using an animal model, mouse with Alzheimer's disease whenthe C29 strain or C3 strain is administered, and the C29 strain was alsoidentified as having the memory improvement effect even in a Y maze taskand a water maze task, and thus, these effects on preventing andtreating dementia were confirmed (See Example 2).

For the present invention, dementia refers to the state, in which abrain function is damaged by various reasons, and also a cognitivefunction such as a memory, linguistic skills, and judgments isconsistently and generally lowered than ever before thereby exhibitingthe negative effects in the daily life, and includes senile dementia,Alzheimer's disease, vascular dementia, Lewy body dementia,frontotemporal dementia, Parkinson's dementia, Huntington's dementia,dementia induced by normal pressure hydrocephalus, dementia induced by ahead injury, dementia induced by a material, and the like.

In addition, as the results of measuring lipid peroxides, superoxidedismutase activity, catalase activity, and glutathione concentrationafter administering the C29 strain or C3 strain to the mice aged 16months for 3 months, the significant superior antioxidant effects wereexhibited as compared with the mice aged 16 months administered withphysiological saline for 3 months, and the decreases of the expressionsof the aging-associated genes were exhibited, and thus, the antioxidantand anti-aging effects were confirmed (see Table 6 and Example 3).

Therefore, the Lactobacillus pentosus var. plantarum C29 andLactobacillus curvatus C3 of the present invention were identified asbeing strains having superior effects for preventing and treatingdementia and an aging.

The morphological features, the physiological features, the analysisresults of the sucrose fermentation, and the composition of cellularfatty acid of the Lactobacillus pentosus var. plantarum C29 of thepresent invention are listed with the features of the known L.plantarium ATCC 14917 and L. pentosus DSM20314, in the following Tables1, 2 and 3.

TABLE 1 Morphological and physiological features of strains C29, L.plantarum ATCC 14917 and L. pentosus DSM20314 Strain L. plantarum L.pentosus Feature C29 ATCC 14917 ™ DSM20314 ™ Morphological feature Shapeof cell Rod Rod Rod Gram-stain Positive Positive Positive Size of cell(μm) 1-1.2 × 0.4-0.6 × 0.8-2 0.8-1 × 2-6 2.2-2.6 Physiological featureGeneration of indol − − − Gas generation of glucose − − − Catalase − − −Oxidase − − − Growth in MRS medium 10° C. + + + 15° C. + + + 45° C. + −− Growth at various pHs pH 3 + − − pH 5 + + + pH 7 + + + Growth underthe presence of NaCl  6% + + +  8% + + + 10% − − − Stability in gastricjuice Stable Unstable Unstable Stability in intestinal juice StableUnstable Unstable G + C (mol %) 50.7 44.1^(a) 46.1^(a) +: positiveresponse; −: negative response ^(a)commercially available from Zanoni,P., Farrow, J. A. E. Philips, B. A., Collins, M. D. (1987) Lactobacilluspentosus (fred, peterson, and anderson) sp. Nov., norn, rev. Int J SystBacteriol 37, 339-341.

TABLE 2 Analysis of sucrose fermentation of lactic acid bacteria usingAPI 20E and API 50CHL L. plantarum ^(a) L. pentosus ^(b) Strain C29ATCC14917 ™ DSM20314 ™ API 20E ONPG − − − TDA − − − IND − − − ADH − − −LDC − − − ODC − − − URE − − − H₂S − − − VP + + + API 50CHL Glycerol −− + L-arabinose + + + D-ribose + + + D-xylose − − + Adonitol − − −D-galactose + + + D-glucose + + + D-fructose + + + D-manose + + +L-rhamnose + − D Dulcitol − − D Manitol + + + Sorbitol + + +α-methyl-D-mannoside + + − α-methyl-D-glucoside − − DN-acetyl-glucosamine + + + Amygdaline + + + Arbutin + + + Esculin + + +Salicine + + + Cellobiose + + + Maltose + + + Lactose + + +Melibiose + + + Sucrose + + + Trehalose + + + Inuline + − −Melezitose + + D Rapinose + + + Gentiobiose + + + D-turanose + + DD-arabitol − + D Gluconate + − + +: positive response; −: negativeresponse; D: variable response ^(a)commercially available from VanReenen, C. A., Dicks, L. M. (1996) Evaluation of numerical analysis ofrandom amplified polymorphic DNA (rapd)-per as a method to differentiatelactobacillus plantarum and lactobacillus pentosus. Curr Microbiol 32,183-187. ^(b)commercially available from Zanoni, P., Farrow, J. A. E.,Phillips, B. A., Collins, M. D. (1987) Lactobacillus pentosus (fred,peterson, and anderson) sp. Nov., norn, rev. Int J Syst Bacteriol 37,339-341.

Any one of the above three lactic acid bacteria did not ferment2-keto-gluconate, 5-keto-gluconate, erythritol, D-arabinose, L-xylose,β-methyl-D-xyloside, L-sorbose, inositol, glycogen, xylitol, D-lyxose,D-tagatose, D-fucose, L-fucose, and L-arabitol.

TABLE 3 Compositions of cellular fatty acid of strains C29, L. plantarumATCC 14917 and L. pentosus DSM20314 L. plantarum ^(a) L. pentosusa Fattyacid Strain C29 ATCC14917 ™ DSM20314TM Saturated fatty acid C_(12:0) 1.1T T C_(14:0) 3.9 4.1 3.9 C_(16:0) 45.5 34.1 20.8 C_(18:0) 5.0 3.3 4.3Unsaturated fatty acid C_(16:1) ω7c 8.7 3.9 5.6 C_(18:1) ω7c 25.5 27.245.1 Branched fatty acid C_(19:0) cyclo ω8c 10.1 8.7 5.7 T: less than 1%of a trace of acid ^(a) L. plantarum: commercially available from VanReenen, C. A., Dicks, L. M. (1996) Evaluation of numerical analysis ofrandom amplified polymorphic DNA (rapd)-per as a method to differentiatelactobacillus plantarum and lactobacillus pentosus. Curr Microbiol 32,183-187. L. pentosus: commercially available from Zanoni, P., Farrow, J.A. E., Phillips, B. A., Collins, M. D. (1987) Lactobacillus pentosus(fred, peterson, and anderson) sp. Nov., norn, rev. Int J Syst Bacteriol37, 339-341.

Also, the morphological features, the physiological features, and theresults of fermentation of sucrose of the Lactobacillus curvatus C3 ofthe present invention are listed along with the features of the known L.curvatus ATCC25601 in the following Tables 4 and 5.

TABLE 4 Morphological and physiological features of strains C3 and L.curvatus ATCC 25601 Feature Strain C3 L. curvatus ATCC25601Morphological feature Shape of cell Rod Rod Gram-stain Positive PositiveSize of the cell (μm) 1-1.2 × 2.2-2.6 0.4-0.6 × 0.8-2 Physiologicalfeature Generation of indol − − Gas generation of glucose − − Catalase −− Oxidase − − Growth in MRS medium 10° C. + + 15° C. + + 45° C. − −Growth at various pHs pH 3 − − pH 5 + + pH 7 + + G + C (mol %) 41.9 +:positive response; −: negative response

TABLE 5 Analysis of sucrose fermentation of lactic acid bacteria usingAPI 20E and API 50CHL Strain C3 L. curvatus ATCC25601 API 20E H₂S − −VP + + API 50CHL L-arabinose − − D-ribose + + D-xylose − −D-galactose + + D-glucose + + D-fructose + + D-mannose + +L-rhamnose + + Sorbitol − − amygdalin − − esculin + + salicine + +Cellobiose + + maltose + + lactose + + melibiose − − sucrose − −trehalose − − melezitose − − rapinose − − +: positive response; −:negative response;

Any one of the above three lactic acid bacteria did not ferment2-keto-gluconate, 5-keto-gluconate, erythritol, D-arabinose, L-xylose,β-methyl-D-xyloside, L-sorbose, inositol, glycogen, xylitol, D-lyxose,D-tagatose, D-fucose, L-fucose, and L-arabitol.

The Lactobacillus pentosus var. plantarum C29 strain and Lactobacilluscurvatus C3 strain of the present invention may be used for preventingand treating aging and dementia, and thus, the present inventionprovides an antioxidant and anti-aging pharmaceutical composition and apharmaceutical composition for preventing or treating dementia, whichinclude a Lactobacillus pentosus var. plantarum C29 strain or aLactobacillus curvatus C3 strain as an active ingredient.

The pharmaceutical composition of the present invention may beadministered orally (e.g., taking medicine by mouth or inhalation) orparenterally (e.g., injection, percutaneous absorption, or rectaladministration), and the injection may be, for example, a venousinjection, a subcutaneous injection, an intramuscular injection, or anintraperitoneal injection. The pharmaceutical composition according tothe present invention may be formulated into a tablet, capsule, granule,fine subtilae, powder, sublingual tablet, suppository, ointment,injection, turbid liquid, suspension, syrup, spray, and the like,according to an administration route. The pharmaceutical compositionsaccording to the present invention in the above-described various formsmay be prepared by the known techniques using a pharmaceuticalacceptable carrier that is generally used for each of the formulations.Examples of the pharmaceutical acceptable carrier include an excipient,binding agent, disintegrating agent, lubricant, preservative,antioxidant, isotonic agent, buffer, coating agent, sweetening agent,solubilizer, base, dispersion, wetting agent, suspending agent,stabilizer, colorant, and the like.

The pharmaceutical composition according to the present inventionincludes the Lactobacillus pentosus var. plantarum C29 strain orLactobacillus curvatus C3 strain of the present invention in the amountof about 0.01 to 100 wt %, depending on their pharmaceuticalformulations.

The specific dose of the pharmaceutical composition of the presentinvention may be varied according to a kind, a body weight, a sex, adegree of the disease of a mammal including a human to be treated, adecision of a practitioner, and the like, and the proper dose accordingto the specific use may be determined by the person ordinary skilled inthe art. Preferably, for an oral administration, 0.001 to 500 mg of anactive ingredient per 1 kg of a body weight per a day is administered,and for a parenteral administration, 0.01 to 200 mg of an activeingredient per 1 kg of a body weight per a day is administered. Morepreferably, 100 mg of an active ingredient per 1 kg of a body weight pera day is administered. The total dose per a day may be administered atone time or several times depending on a degree of a disease, a judgmentby a practitioner and the like.

The present invention also provides a health dietary supplement havingan antioxidant and anti-aging effects and a health dietary supplementfor preventing or improving dementia, which includes a C29 strain or aC3 strain as an active ingredient.

A kind of the health dietary supplement of the present invention is notspecifically limited, and the health dietary supplement of the presentinvention may be in a form of an oral-type formulation, such as, apowder, granule, table, capsule, suspension, emulsion, and syrup, or maybe added to a general food, such as, a candy, cracker, gum, ice cream,noodle, bread, and beverage.

The health dietary supplement of the present invention may be preparedby properly using a filler, extender, binder, wetting agent,disintegrating agent, sweetening agent, flavoring agent, preservative,surfactant, lubricant, excipient, and the like in a routine manneraccording to its forms.

The content of a C29 strain or C3 strain for the preparation of theabove-described health dietary supplement is different according to aform of a health dietary supplement, but the content thereof may beapproximately 0.01 to 100 wt %.

In addition, the present invention provides a composition having anantioxidant and anti-aging effect and a composition for preventing orimproving dementia, which include a fermentation composition that isfermented with a C29 strain or C3 strain, as an active ingredient.

In the present invention, the fermentation composition includes afermentation composition of a soybean or defatted soybean, afermentation composition of kalopanax, a fermentation composition ofginseng, and a fermentation composition of Codonopsis lanceolata.

In the present invention, a water suspension of the powder of thesoybean or defatted soybean means to one prepared by adding 5 to 15times water to the powder's weight to the powder of the dried soybean ordefatted soybean and suspending the powder in the water, but the presentinvention is not limited thereto. A type of soybean milk prepared bygrinding the soybean soaked in water may be used, as long as itcorresponds to the objects of the present invention.

In the present invention, the kalopanax, ginseng and Codonopsislanceolata may be in a form of an extract or essence, and preferably, atype of the extract prepared by a hydrothermal extraction, ethyl alcoholextraction or mixed extraction may be used, but the present invention isnot limited thereto. In order to increase the extraction efficiency ofthe above-described extract, it may be ground or powdered, and thegrinding and pulverization process may be conducted according to theconventional extraction method well-known in the art. For example, awater extraction method, alcohol extraction method, organic solventextraction method and supercritical extraction method, and the like, maybe used, and preferably the water extraction method is used, but thepresent invention is not limited thereto.

As an extraction solvent used in the above-described alcohol extractionmethod, low alcohol having 1 to 6 carbon atoms, and the like, such asmethanol, ethanol, propanol, isopropanol, and butanol, may be used, andas an extraction solvent used in the above-described organic solventextraction method, an organic solvent such as acetone, ether, benzene,chloroform, ethylacetate, methylene chloride, hexane, hydrochloric acid,acetic acid, formic acid, citric acid, cyclohexane and petroleum ether;or a mixture thereof may be used.

At this time, the rate of the extraction solvent added at the time ofextraction is not specifically limited, but 2 to 20 times (based on theweight) of the extraction solvent with respect to the dry weight ofkalopanax, ginseng, or Codonopsis lanceolata may be used. In order toincrease the extraction efficiency, preferably, the extraction may berepeated several times, for example, 2 times or more by using 5 times to15 times (based on the weight) of the extraction solvent with respect tokalopanax, ginseng or Codonopsis lanceolata.

At this time, an extraction temperature is preferably 50 to 110° C., andmore preferably, 70 to 100° C. An extraction time varies according tothe extraction temperature, but may be 1 to 48 hours, and preferably 2to 8 hours. In addition, when it is stirred with a shaker at the time ofextraction, the extraction efficiency may be more increased.

The extract may be prepared by a decompression distillation method orthin film distillation method.

In the present invention, the effects of the soybean or defatted soybeanfermentation composition fermented by inoculating a C29 strain or C3strain, the kalopanax fermentation composition, the ginseng fermentationcomposition, and the Codonopsis lanceolata fermentation composition onimproving the memories of mice are confirmed in a passive avoidanceresponse task by using the mice, an animal model with Alzheimer'sdisease, and thus, the effects for preventing or treating dementia areconfirmed (see Example 5).

In the present invention, when the C29 strain or C3 strain is inoculatedon the above-described extract, the extract is used after heating theextract at the temperature of 100° C. or more for 15 minute to 1 hourfor a sterilization to inhibit the growth of spoilage bacteria at thetime of the inoculation.

Although the inoculating amount of the C29 strain or C3 strain variesaccording a kind of the extract used in the fermentation, theinoculating amount thereof is to be 1×10⁸ CFU/ml or more and afermentation temperature is preferably 20 to 40° C. Although afermentation time is not specifically limited as long as it correspondsto the objects of the present invention, the fermentation time may be 10to 30 hours after inoculating the C29 strain or C3 strain. In this case,when it is fermented for 10 hours or more, the fermentation compositionis not sufficiently made, and when it is fermented for 30 hours andmore, an organic acid is made much so as to generate strong sour tasteand thus decrease a mouthfeel, and therefore, it is preferable toferment it within the range of the fermentation time as mentioned above.

In addition, in the present invention, various fermentation food may beprepared according to the materials used in the fermentation; and forexample, a fermentation beverage of lactic acid bacteria such as ayogurt may be prepared by inoculating a C29 strain or C3 strain to drymilk or milk, and then, fermenting it by the manner as above.

Advantageous Effects

It is confirmed that the Lactobacillus pentosus var. plantarum C29strain or Lactobacillus curvatus C3 strain of the present invention hasthe superior effects on preventing and improving aging and dementia, andthus, they can be usefully utilized in the prevention or treatment ofaging and dementia. Therefore, the pharmaceutical composition and thehealth dietary supplement including the Lactobacillus pentosus var.plantarum C29 strain or Lactobacillus curvatus C3 strain of the presentinvention can be effectively used for preventing or treating aging anddementia. Since the strains which are present in Kimchi intakenroutinely are an active ingredient, it can be used without any concernfor side effects or toxicity. In addition, since the fermentationcompositions are prepared by inoculating the Lactobacillus pentosus var.plantarum C29 strain or Lactobacillus curvatus C3 strain of the presentinvention, they can be effectively utilized as the compositions forpreventing or treating aging and dementia.

EXAMPLES

Hereinafter, the present invention will be described in more detail withreference to Examples. These Examples are only to illustrate theinvention, and it is self-evident to the skilled person in the art thatthe scope of the present invention is not to be limited to suchExamples.

Example 1 Isolation of Lactic Acid Bacteria

Cabbage Kimchi was suspended in MRS broth, the supernatant thereof wasinoculated on MRS agar medium, and then, the medium thereof wasanaerobically cultured at a temperature of 37° C. for 24 hours. Sincethen, the colony being grown out was selected and gram-stained, and 16SrDNA thereof was analyzed, and then a lactobacillus strain was isolated.

In addition, human feces were suspended in GAM broth (NissuiPharmaceutical Company, Ltd., Japan), the supernatant thereof wasinoculated on BL agar medium (Nissui Pharmaceutical) and then, themedium thereof was anaerobically cultured at 37° C. for 48 hours. Sincethen, the colony being grown out was selected and gram-stained, and 16SrDNA thereof was analyzed, and then, the lactobacillus andBifidobacterium strains were isolated.

The isolated strains are as follows:

1) Lactic acid bacteria used by isolating from Kimchi

-   -   Leuconostoc mesenteroides C1    -   Leuconostoc kimchii C2    -   Lactobacillus curvatus C3    -   Lactobacillus brevis C4    -   Lactobacillus brevis C5    -   Lactococcus plantarum C6    -   Leuconostoc citreum C7    -   Pediococcus pentosus C8    -   Lactobacillus acidophilus C9    -   Lactobacillus lactis C10    -   Lactobacillus helveticus C11    -   Lactobacillus plantarum C12    -   Lactobacillus casei C13    -   Lactobacillus sakei C14    -   Lactobacillus pentosus C15    -   Lactobacillus sakei C21    -   Lactobacillus sakei C22    -   Lactobacillus sakei C23    -   Lactobacillus plantarum C24    -   Lactobacillus plantarum C25    -   Lactobacillus plantarum C26    -   Lactobacillus pentosus C27    -   Lactobacillus pentosus C28    -   Lactobacillus pentosus var. plantarum C29    -   Lactobacillus sakei C30

2) Lactic acid bacteria used by isolating from human digestive tract

-   -   Bifidobacterium breve C16    -   Bifidobacterium longum C17    -   Bifidobacterium adolescentis C18    -   Bifidobacterium bifidum C19    -   Latobacillus acidophilus C20

Example 2 Identification of Anti-Dementia Effects

In order to identify lactic acid bacteria having anti-dementia effectsamong 30 lactic acid bacteria isolated from Kimchi and feces, anexperiment was performed by using the above-described C1 to C30 strainsand laboratory animals.

All animals used in the experiment were the male ICR-based mice (28 to30 g), and the experiment was performed in accordance with Guide for theCare and Use of Laboratory Animal (NIH publication No. 85-23). 5 and 6laboratory animals were housed in a cage and were leaved to freelyaccess to the food. The temperature in the cage was 23±1° C., themoisture was 60±10%, and 12 hours of day and night (07:30˜19:30) werealways maintained.

2-1. Passive Avoidance Task Test

An experimental box (50×15×40 cm, electrofiable frid floor) as anexperimental equipment was divided into two sections by using apartition, and it is designed so that when entering one side into theopposite side via a small entrance, the entrance was closedautomatically. When an animal was put into one side of the sectiondivided by the partition with turning on the light, it looked aroundfollowed entering into the dark section without any light, the entrancewas automatically closed, immediately foot shock was made by flowing0.25 mA of an electric current through stainless grid of a floor for onesecond. At the next day, the latency from the time that the laboratoryanimal was put into the section turning on the light to the time thatthe animal was passed over the dark section and then the entrance wasclosed was determined. The latencies until the mouse enters into thedark section like this were determined and compared for the control andtest groups. The maximal limitation time was set to 300 seconds, whereinif the mouse did not enter into the dark section until over 300 seconds,the passive avoidance response latency was determined as 300 seconds. Itwas determined that greater the time until the animal passes over thedark section and the entrance was closed, the memory for passiveavoidance through learning was well remained.

30 kinds of C1 to C30 lactic acid bacteria used in the experiment wereadministered to the animal model with dementia in a number of 1×10¹⁰ CFUone per 1 day for 2 days. Scopolamine (0.9 mg/kg) was administered at 1hour after the last administration of lactic acid bacteria. As a result,as can be identified in FIG. 3, C29 of lactic acid bacteria used in theexperiment best maintained the memory for the passive avoidance andexhibited the effects superior to Tacrin (TAC, 10 mg/kg), the treatingagent of dementia, and it was the order of C3, and then C24.

C29 lactic acid bacteria identified as having the best effects wereadministered to the mouse in 1×10⁹ and 1×10¹⁰ CFU one per 1 day for two(2) days. Scopolamine (0.9 mg/kg) was administered at one hour after thelast administration of lactic acid bacteria. As a result, as identifiedin FIG. 4, C29 exhibited the effects in a concentration-dependentmanner.

In addition, in order to identify the effect for improving dementia inthe animal, hippocampus of a brain was isolated and was homogenized byadding 100 μg of RIPA buffer (Gibco) with protease inhibitor cocktail.After centrifuging it at 4° C., 13000 rpm for 15 minutes, p-CREB, CREB,BDNF and β-actin were measured by an immunoblotting method, while thesupernatant was stored at −80° C.

Firstly, the supernatant was taken and subjected to an electrophoresison SDS 10% (w/v) polyacrylamide gel for an hour and a half (sample, 50μg). The gel subjected to electrophoresis was transferred onto anitrocellulose paper at 100 V, 400 mA for 1 hour and 10 minutes, thetransferred nitrocellulose paper was blocked by 5% defatted milk for 30minutes and then washed with PBS-Tween three times each of 5 minutes,was reacted with the first antibody (Santa Cruz Biotechnology, USA) as1:100 overnight. And then, after washing it three times with each of 10minutes, the secondly antibody (Santa Cruz Biotechnology, USA) wasreacted as 1:1000 for 1 hour and 20 minutes. And then, it was washedthree times for 15 minutes, and was developed by emitting fluorescence.As a result, as can be confirmed in FIG. 5, it could be determined thatp-CREB and BDNF which were reduced by only the administration ofscopolamine were recovered in the group administered by C29simultaneously with scopolamine as compared with the animal groups ofmodels with dementia administered by only scopolamine. This fact showsthat C29 lactic acid bacteria have the memory improvement effect.

The experimental results as above described show that the C29 and C3lactic acid bacteria exhibit the dementia improvement effect via animprovement of the memory.

2-2. Y-Maze Task

A Y-maze task measuring equipment had a shape of alphabet Y extendingthree arms, in which all the branches had 25 cm of a length, 14 cm of aheight, and 5 cm of a width, and were positioned in the same angle. Ahead part of the laboratory animal is headed for the end of a path ofY-maze and let it go around a passage freely for 8 minutes. Afterrecording a movement of the animal, if hind legs of the animal enteredthe passage, it is considered that the animal is arm entry. The movementof the animal is represented by an alternation, which is defined that ifthe animal passes three (3) passages continuously, it is defined asbeing one alternation. An amount of a spontaneous alternation isrepresented by a percent of the real alternation and the maximalpossible alternation (i.e., a value obtained by deducting 2 from thetotal alternation).

The C29 which is the best one of lactic acid bacteria used in theexperiments was administered to the mouse in 1×10⁹ and 1×10¹⁰ CFU oneper 1 day for two (2) days. Scopolamine (0.9 mg/kg) was administered atone hour after the last administration of lactic acid bacteria.

As a result, as can be identified in FIG. 6, the test group administeredby the C29 exhibited the memory improvement effect in aconcentration-dependent manner as compared with the control administeredby scopolamine only.

2-3. Water Maze Task

To a circle type of water tank (a diameter of 100 cm and a height of 35cm), water that was made foggy by putting dry milk so as not to see aplatform equipped in water of 23° C. was filled in a depth of 15 cm. Inthe case of using a mouse, a platform (a diameter of 4.5 cm and a heightof 14.5 cm) was placed in the center of one fan shape of 4-dividedshapes of water tank so that the top of the platform is placed below 0.5cm of the surface of water. This device was installed in the laboratoryhaving a mark which can identify the position. A training trial waspracticed three times per a day for five days in consequentially. Oncethe mouse found the platform, it is allowed to stay for 10 sec, and backto the original cage, and after 5 min, the next trial was practiced. Ifthe mouse did not find the platform within 120 sec, it is allowed tostay in the platform for 10 sec, and then finished the trial. A probetest was practiced to the animal that the trial was finished at 24 hrsafter the final trial. At this time, the platform was removed from thepool, and the time staying in the 4-divided circle that the platform wasplaced during 90 sec was measured to represent it as a percentage.

A swimming time was measured daily while administering the best C29lactic acid bacteria in the amount of 1×10⁹ and 1×10¹⁰ CFU among thelactic acid bacteria used in the experiment once per day for 4 days.Scopolamine (0.9 mg/kg) was administered at 1 hour after the firstadministration.

As a result, the C29 lactic acid bacteria exhibited the memoryimprovement effect in a concentration-dependent manner, as can be seenin FIG. 7.

Example 3 Identifications of Anti-Oxidation, Anti-Aging andAnti-Dementia Effect

In order to identify the anti-oxidation, anti-aging and anti-dementiaeffect, three lactic acid bacteria C29, C3, C24 (1×10⁹ CFU,respectively) were administered for five days for 12 weeks, and theanti-aging effect of the lactic acid bacteria and aging-associated geneAKT, FOXO3, NF-κB (p65), mTorr phosphate body in a large intestine thatthe progress of oxidation reaction is fast, were measured. Beta-actinwas measured as a comparative gene. Also, the memory improvement effectwas measured.

1) Lipid Peroxide Analysis

To 100 mg of the large intestine tissue of the laboratory animal, 250 μlof RIPA buffer containing protease inhibitor cocktail was added tohomogenate. Thereafter, it was centrifuged for 15 min at 4° C., 13000rpm, and then the surfactant was used in the lipid peroxidation analysiswhile storing −80° C.

The lipid peroxidation degree in the large intestine tissue was analyzedby using TBARS analysis kit (Cayman chem., USA). 100 μl of homogenate ofthe large intestine tissue was placed in 5 ml of a polypropylenescrew-cap centrifugal tube, and then 100 μl of SDS solution was addedand shaken lightly. 4 ml of color reagent was added to the tube, andthen put into boiling water for 1 hour to stop the reaction. Thereafter,it was centrifuged for 10 min at 4° C., 13000 rpm, and then allowed tostand for 30 min at the room temperature, and measured the absorbance at540 nm using an ELISA reader. The standard cure was made by usingmalonaldehyde (MDA) as a standard material, and the amount of MDAproduced from this was measured.

2) Superoxide Dismutase (SOD) Activity

The Cu, Zn-SOD activity was measured by using xanthineoxidase-cytochrome C system. 2. 4 ml of 50 Mm potassium phosphate (pH7.8, containing 0.1 mM EDTA), 0.3 ml of 0.1 mM pericytochrome C, 0.2 mlof 1% deoxycholate, 0.1 ml of 1.5 mM potassium cyanate, 0.3 ml of 0.5 mMxanthine and 20 ml of xanthine oxidase were thoroughly mixed, and thereduction rate of pericytochrome C was measured at 25° C., 550 nm. 1unit of SOD was defined as the amount to inhibit 50% reduction ofcytochrome C.

3) Catalase Activity

To 2 ml of 50 mM phosphate buffer (pH 7.0), 100 μl of an enzyme sourcewas added, and 1 ml of 10 mM H₂O₂ solution was added to measure thereduction of the absorbance for 2 min. 1 unit was defined as the amountof the enzyme which decomposes 1 mol H₂O₂ for 1 min.

4) Glutathione (GSH)

A GSH concentration was measured by diluting a sample with a phosphatebuffer and adding o-phthaldehyde, shaking for 15 min, and measuring thefluorescence at 345 nm of an excitation wavelength and 425 nm of aradiation wavelength.

As the results of four experiments as above, all 3 strains used in theexperiments exhibited excellent anti-oxidation and anti-aging results,as listed in the following Table 6. The most excellent stain was C29,and then in the order of C24 and C3.

TABLE 6 Activity of the enzyme (mol/min/mg) Malon Superoxide aldehydeGlutathione dismutase Catalase (μmol/mg of (μg/mg of Group (mol/min/mg)(mol/min/mg) protein) protein) Administering physiological saline 2.8 ±0.6 6.0 ± 0.6 2.5 ± 0.9 3.9 ± 0.2 to mouse aged 2 months (for threemonths) Administering physiological saline 0.9 ± 0.2 0.8 ± 0.5 9.4 ± 0.21.9 ± 1.3 to mouse aged 16 months (for three months) Administering C29to mouse aged 1.6 ± 0.4 4.5 ± 1.0 5.2 ± 1.9 3.9 ± 0.5 16 months (forthree months) Administering C3 to mouse aged 1.8 ± 0.3 4.2 ± 1.2 5.3 ±1.2 2.8 ± 0.9 16 months (for three months) Administering C24 to mouseaged 1.9 ± 0.6 4.1 ± 1.6 4.2 ± 2.1 4.0 ± 1.4 16 months (for threemonths)

In addition, to 100 mg of larger intestine tissue of the laboratoryanimal, 250 μl of RIPA buffer (Gibco) including protease inhibitorcocktail was added to homogenate. It was centrifuged for 15 min at 4°C., 13000 rpm, and then, phosphor-FOXO3, phosphor-p65, p65,phosphor-mTorr, phosphor-AKT and β-actin were measured via animmunoblotting method while storing the supernatant at −80° C.

The supernatant was taken and subjected to the electrophoresis in a SDS10% (w/v) polyacrylamide gel for 1 hr and 30 minutes (sample, 50 μg).The gel subjected to the electrophoresis was transferred to anitrocellulose paper at 100 V, 400 mA for 1 hour and 10 minutes, thetransferred nitrocellulose paper was blocked with 5% defatted milk for30 minutes and then was washed with PBS-Tween three times with each of 5minutes, reacted with the first antibody (Santa Cruz Biotechnology, USA)at 1:100 overnight, washed three times with each of 10 minutes, andreacted with the secondly antibody (Santa Cruz Biotechnology, USA) at1:1000 for 1 hour and 20 minutes. After then, it was washed three timeswith each of 15 minutes, was development with emitting fluorescence.

The cell treated in the same method as the above method, except fortreating it with the active ingredient and LPS, was used as a control.As a result, as illustrated in FIG. 8, it could be seen that in the testgroup treated with the C29 or C3, the expressions of p-p65, p-FOXO3,p-mTor, p-AKT and the like were significantly reduced as compared withthe untreated group, and it showed the antioxidant or anti-aging effectsby C29 or C3.

5) Y-Maze Task

A Y-maze task equipment has a shape of alphabet Y extending three arms,wherein the each branch has 25 cm of a length, 14 cm of a height, and 5cm of a width and placed with the same angle. A head part of thelaboratory animal is headed for the end of a path of Y-maze and let itgo around the path freely for 8 minutes. After recording a movement ofthe animal, when hind legs of the animal entered the passage, it isconsidered that the animal is arm entry. The movement of the animal isrepresented by alternation, which is defined that when the animal passesthree (3) passages continuously, it is defined as one alternation. Aspontaneous alternation is represented as a percent of the realalternation and the maximal possible alternation (i.e., a value obtainedby deducting 2 from the total alternation).

In this task, the C29 lactic acid bacteria, C3 lactic acid bacteria andC24 lactic acid bacteria were administered to the mice aged 16 months in1×10⁹ CFU one per 1 day for two (2) days. In this task, since the memoryof the aged mice was lower than that of young mice, scopolamine was notadministered.

As a result, as can be identified in FIG. 9, the C29 lactic acidbacteria was the best in the memory improvement effect of the agedmouse, and then was in the order of the C3 lactic acid bacteria and C24lactic acid bacteria.

6) Morris Water Maze Task

To a circle type of water tank (a diameter of 100 cm and a height of 35cm), water that was made foggy by putting dry milk so as not to see aplatform equipped in water of 23° C. was filled in a depth of 15 cm. Inthe case of using a mouse, a platform (a diameter of 4.5 cm and a heightof 14.5 cm) was placed in the center of one fan shape of 4-dividedshapes of water tank so that the top of the platform is placed below 0.5cm of the surface of water. This device was installed in the laboratoryhaving a mark which can identify the position. A training trial waspracticed three times per day for five days 6 in consequentially. Oncethe mouse found the platform, it is allowed to stay for 10 sec, and backto the original cage, and after 5 min next trial was practiced. If themouse did not find the platform within 120 sec, it is allowed to stay inthe platform for 10 sec, and then finished the trial. A probe test waspracticed to the animal that the trial was finished at 24 hrs after thefinal trial. At this time, the platform was removed from the pool, andthe time staying in the 4-divided circle that the platform was placedduring 90 sec was measured to represent it as a percentage.

A swimming time was measured daily while administering the C29 lacticacid bacteria, C3 lactic acid bacteria and C24 lactic acid bacteria tothe mice aged 16 months in the amount of 1×10⁹ CFU once per a day for 4days. In this test, since the memory of the aged mice was lower thanthat of young mice, scopolamine did not administered.

As a result, as can be identified in FIG. 10, the C29 lactic acidbacteria were the best in the memory improvement effect of the agedmouse, and then were in the order of the C3 lactic acid bacteria and C24lactic acid bacteria.

Example 4 Identifications of C29 and C3 Lactic Acid Bacteria

In order to identify the C29 strain and C3 strain verified as having thesuperior antioxidant and anti-aging effects and dementia improvementeffects in the above tasks, a phylogenetic analysis was performedthrough the comparison of 16S rDNA gene sequences

When the rDNA base sequences were compared with each other using a BLASTsimilarity search program, and then, was proceeded an alignment ofmultiple sequences with the 16S rDNA gene sequences of variouslactobacillus sp. Strains, and their positions were determined in aphylogenetic tree, since the C29 lactic acid bacteria exhibited at least99.9% of homologe with Lactobacillus plantarum strain BIM B-536 andLactobacillus pentosus strain LS3, they were named as Lactobacillusplantarum var. plantarum C29 and was deposited to the DepositaryAuthority, Korean Culture Center of Microorganisms (“KCCM”) as a DepositNo. KCCM11291P, on Jul. 9, 2012. In addition, since the C3 lactic acidbacteria exhibited at least 99.9% of homologe with Lactobacilluscurvatus, they were named as Lactobacillus curvatus C3, and weredeposited to Deposit Authority, Korean Culture Center of Microorganisms(KCCM) as a Deposit No. KCCM43009, on Jul. 9, 2012.

Example 5 Identification of Anti-Dementia Effect of C29 or C3 StrainFermentation Composition

In order to identify the anti-dementia effects of a soybean or defattedsoybean fermentation composition fermented with a C29 or C3 strain, akalopanax fermentation composition, a ginseng fermentation composition,and a Codonopsis lanceolata fermentation composition, a passiveavoidance task test using the laboratory animals was performed in thesame method as Example 2.

5-1. Preparation of Fermentation Composition

10 g of a powder of the soybean or defatted soybean was suspended in 90ml of water and sterilized, and 10 ml of the C29 or C3 strain was addedin the amount of 1×10⁸ CFU/0.1 ml thereto, and then, was cultured for 24hrs.

10 g of each of a water extract of kalopanax, a water extract of ginsengand a water extract of Codonopsis lanceolata was suspended in 90 ml ofwater and sterilized, and 10 ml of the C29 or C3 strain was added in theamount of 1×10⁸/0.1 ml, and then, was cultured for 24 hrs.

5-2. Passive Avoidance Task Test

0.1 ml of each of the soybean or defatted soybean fermentationcomposition, kalopanax fermentation composition, ginseng fermentationcomposition and Codonopsis lanceolata fermentation composition preparedby said method was added to the dementia model, mice once per 1 day fortwo (2) days. Scopolamine (0.9 mg/kg) was administered at one hour afterthe last administration of lactic acid bacteria. As a result, as can beidentified in FIG. 12, the soybean fermentation composition fermented byC29 maintained the best in memory for the passive avoidance andexhibited superior effect as compared with the treating agent ofdementia, Tacrin (TAC, 10 mg/kg), and followed by the ginsengfermentation composition fermented by C29, soybean fermentationcomposition fermented by C3, and Codonopsis lanceolata fermentationcomposition fermented by C29 in order. It shows that the fermentationcomposition fermented by the C29 or C3 strain has the memory improvementeffect.

The results of the above-described tasks show that the fermentationcomposition fermented by the C29 or C3 strain exhibits the dementiaimprovement effect by improving the memory.

The invention claimed is:
 1. A composition comprising: a fermentationproduct as an active ingredient, wherein the fermentation productcomprises Lactobacillus pentosus var. plantarum C29 strain (depositnumber: KCCM11291P) and is obtained by inoculating a specific substratewith Lactobacillus pentosus var. plantarum C29 strain (deposit number:KCCM11291P) and culturing it for 10 to 30 hours, wherein the specificsubstrate is selected from the group consisting of soybean seeds anddefatted soybean seeds.
 2. The composition of claim 1, furthercomprising a pharmaceutically acceptable carrier selected from the groupconsisting of an excipient, a binding agent, a disintegrating agent, alubricant, a preservative, an antioxidant, an isotonic agent, a buffer,a coating agent, a sweetening agent, a solubilizer, a base, adispersion, a wetting agent, a suspending agent, a stabilizer, acolorant, and combinations thereof.
 3. An injectable solution comprisingthe composition of claim
 1. 4. The composition of claim 1, wherein thecomposition is in a form selected from the group consisting of tablets,capsules, granules, fine subtilae, powders, sublingual tablets,suppositories, ointments, injections, turbid liquids, suspensions,syrups, and sprays.
 5. A food product comprising the composition ofclaim 1, wherein the food product is selected from the group consistingof candy, cracker, gum, ice cream, noodle, bread, and beverage.
 6. Amethod of improving cognitive function or treating cognitive impairmentcomprising administering to a subject in need thereof an effectiveamount of the composition of claim
 1. 7. A method of improving cognitivefunction or treating cognitive impairment comprising administering to asubject in need thereof an effective amount of the composition ofclaim
 1. 8. A composition comprising: a fermentation product as anactive ingredient, wherein the fermentation product comprisesLactobacillus pentosus var. plantarum C29 strain (deposit number:KCCM11291P) and is obtained by inoculating a specific substrate withLactobacillus pentosus var. plantarum C29 strain, wherein the specificsubstrate comprises defatted soybean powder.
 9. The composition of claim8, wherein the specific substrate is sterilized prior to inoculationwith Lactobacillus pentosus var. plantarum C29 strain.
 10. Thecomposition of claim 8, wherein the specific substrate is sterilized byheating to a temperature of 100° C. or more for 15 minutes to 1 hour.11. An injectable solution comprising the composition of claim
 8. 12.The composition of claim 8, wherein the composition is in a formselected from the group consisting of tablets, capsules, granules, finesubtilae, powders, sublingual tablets, suppositories, ointments,injections, turbid liquids, suspensions, syrups, and sprays.
 13. A foodproduct comprising the composition of claim 8, wherein the food productis selected from the group consisting of candy, cracker, gum, ice cream,noodle, bread, and beverage.
 14. The composition of claim 8, furthercomprising a pharmaceutically acceptable carrier.